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Thromb Haemost 2007; 97(01): 21-26
DOI: 10.1160/TH06-04-0211
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Relatively increased von Willebrand factor activity after off-pump coronary artery bypass graft surgery

Bernard Lo
1   Department of Anesthesiology
,
Arno P. Nierich
3   Department of Thoracic Anesthesiology and Intensive Care, Isala Clinics, Zwolle
,
Cor J. Kalkman
1   Department of Anesthesiology
,
Rob Fijnheer
2   Department of Hematology, University Medical Center Utrecht, Utrecht
4   Department of Internal Medicine, Jeroen Bosch Center, ‘s Hertogenbosch, The Netherlands
› Author AffiliationsFinancial support: This study is a substudy of the Octopus-trial that was funded by grant OG 98–026 from the Netherlands National Health Insurance Council. Additional funding for laboratory research was provided by Medtronic Inc.
Further Information

Publication History

Received 15 April 2006

Accepted after resubmission 22 November 2006

Publication Date:
28 November 2017 (online)

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Summary

High shear forces can induce structural changes in the shape of the von Willebrand factor (VWF) molecule, making it more sensitive for ADAMTS-13, a specific VWF protease. This leads to proteolysis of the highest-molecular-weight multimers, which are the most effective in platelet-mediated hemostasis under conditions of high shear stress. The use of cardiopulmonary bypass (CPB) is accompanied with high shear forces and could therefore lead to diminished VWF activity. Therefore, we studied VWF activity in patients undergoing myocardial revascularization. We enrolled 60 patients undergoing coronary artery bypass graft (CABG) surgery with and without CPB (30 in each group). ADAMTS-13 activity, VWF antigen (VWF:Ag) and propeptide levels were measured directly before and after the procedure. VWF activity was determined using both the ristocetin cofactor activity (VWF:Rcof) and collagen binding (VWF:CB) assays. VWF:Rcof and VWF:CB, both corrected for VWF:Ag, were significantly increased after the procedure in the off-pump group (p<0.001 and p=0.05, respectively), but not in the CPB group. Postoperative VWF:Ag and VWF-propeptide levels significantly increased in both groups. ADAMTS-13 activity increased after both types of surgery after correction for hemodilution. Postoperative VWF: Rcof levels correlated with postoperative D-dimer levels (p=0.025) and were associated with early cognitive decline in the off-pump group (p=0.025). Our data indicate that VWF activity is increased after off-pump CABG, but not after CABG with CPB. Since release of VWF is comparable in both groups, shear stress-induced proteolysis due to the use of CPB may be responsible for the decreased VWF activity.

Keywords

Von Willebrand factor - hypercoagulability - proteases / inhibitors - acquired coagulation disorders
 

  • References

  • 1 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424.
    CrossrefPubMedGoogle Scholar
  • 2 Moake JL, Turner NA, Stathopoulos NA. et al Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 78: 1456-61.
    CrossrefPubMedGoogle Scholar
  • 3 Tsai HM, Nagel RL, Hatcher VB. et al Multimeric composition of endothelial cell-derived von Willebrand factor. Blood 1989; 73: 2074-6.
    CrossrefPubMedGoogle Scholar
  • 4 Siedlecki CA, Lestini BJ, Kottke-Marchant KK. et al Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 1996; 88: 2939-50.
    CrossrefPubMedGoogle Scholar
  • 5 Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood 1994; 83: 2171-9.
    CrossrefPubMedGoogle Scholar
  • 6 Vincentelli A, Susen S, Le Tourneau T. et al Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-9.
    CrossrefPubMedGoogle Scholar
  • 7 Rinder CS, Bohnert J, Rinder HM. et al Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991; 75: 388-93.
    CrossrefPubMedGoogle Scholar
  • 8 Holloway DS, Summaria L, Sandesara J. et al Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients. Thromb Haemost 1988; 59: 62-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Gelb AB, Roth RI, Levin J. et al Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding. Am J Clin Pathol 1996; 106: 87-99.
    CrossrefPubMedGoogle Scholar
  • 10 van Dijk D, Nierich AP, Jansen EW. et al Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001; 104: 1761-6.
    CrossrefPubMedGoogle Scholar
  • 11 van Dijk D, Jansen EW, Hijman R. et al Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. J Am Med Assoc 2002; 287: 1405-12.
    CrossrefPubMedGoogle Scholar
  • 12 Nathoe HM, van Dijk D, Jansen EW. et al A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med 2003; 348: 394-402.
    CrossrefPubMedGoogle Scholar
  • 13 Murdock PJ, Woodhams BJ, Matthews KB. et al von Willebrand factor activity detected in a monoclonal antibody-based ELISA: an alternative to the ristocetin cofactor platelet agglutination assay for diagnostic use. Thromb Haemost 1997; 78: 1272-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Borchiellini A, Fijnvandraat K, ten Cate JW. et al Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood 1996; 88: 2951-8.
    CrossrefPubMedGoogle Scholar
  • 15 van der Plas RM, Gomes L, Marquart JA. et al Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains. Thromb Haemost 2000; 84: 1005-11.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Moake JL, Weinstein MJ, Troll JH. et al Direct radioimmune detection in human plasma of the association between factor VIII procoagulant protein and von Willebrand factor, and the interaction of von Willebrand factor-bound procoagulant VIII with platelets. Blood 1983; 61: 1163-73.
    CrossrefPubMedGoogle Scholar
  • 17 Kokame K, Nobe Y, Kokubo Y. et al FRETSVWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 2005; 129: 93-100.
    CrossrefPubMedGoogle Scholar
  • 18 Lo B, Fijnheer R, Nierich AP. et al Activation of hemostasis is associated with early cognitive decline after off-pump coronary artery bypass surgery. J Thromb Haemost 2005; 3: 2114-7.
    CrossrefPubMedGoogle Scholar
  • 19 Mariani MA, Gu YJ, Boonstra PW. et al Procoagulant activity after off-pump coronary operation: is the current anticoagulation adequate?. Ann Thorac Surg 1999; 67: 1370-5.
    CrossrefPubMedGoogle Scholar
  • 20 Palanzo DA, Zarro DL, Manley NJ. et al Effect of surface coating on platelet count drop during cardiopulmonary bypass. Perfusion 1999; 14: 195-200.
    CrossrefPubMedGoogle Scholar
  • 21 Mueller XM, Tevaearai HT, Horisberger J. et al Smart suction device for less blood trauma: a comparison with Cell Saver. Eur J Cardiothorac Surg 2001; 19: 507-11.
    CrossrefPubMedGoogle Scholar
  • 22 Liu L, Choi H, Bernardo A. et al Platelet-derived VWF-cleaving metalloprotease ADAMTS-13. J Thromb Haemost 2005; 3: 2536-44.
    CrossrefPubMedGoogle Scholar
  • 23 Uemura M, Tatsumi K, Matsumoto M. et al Localization of ADAMTS13 to the stellate cells of human liver. Blood 2005; 106: 922-4.
    CrossrefPubMedGoogle Scholar
  • 24 Turner N, Nolasco L, Tao Z. et al Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost 2006; 4: 1396-404.
    CrossrefPubMedGoogle Scholar
  • 25 Mannucci PM, Parolari A, Canciani MT. et al Opposite changes of ADAMTS-13 and von Willebrand factor after cardiac surgery. J Thromb Haemost 2005; 3: 397-9.
    CrossrefPubMedGoogle Scholar
  • 26 Kremer Hovinga JA, Mottini M, Lammle B. Measurement of ADAMTS-13 activity in plasma by the FRETS-VWF73 assay: comparison with other assay methods. J Thromb Haemost 2006; 4: 1146-8.
    CrossrefPubMedGoogle Scholar
  • 27 Perrin EJ, Ray MJ, Hawson GA. The role of von Willebrand factor in haemostasis and blood loss during and after cardiopulmonary bypass surgery. Blood Coagul Fibrinolysis 1995; 6: 650-8.
    CrossrefPubMedGoogle Scholar
  • 28 Weinstein M, Ware JA, Troll J. et al Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. Blood 1988; 71: 1648-55.
    CrossrefPubMedGoogle Scholar
  • 29 Hackmann T, Gascoyne RD, Naiman SC. et al A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery. N Engl J Med 1989; 321: 1437-43.
    CrossrefPubMedGoogle Scholar
  • 30 Perutelli P. Proteolysis of von Willebrand factor is increased during cardiopulmonary bypass. Thromb Res 2001; 102: 467-73.
    CrossrefPubMedGoogle Scholar
  • 31 Weerasinghe A, Taylor KM. The platelet in cardiopulmonary bypass. Ann Thorac Surg 1998; 66: 2145-52.
    CrossrefPubMedGoogle Scholar
  • 32 Kestin AS, Valeri CR, Khuri SF, Loscalzo J, Ellis PA, MacGregor H. et al The platelet function defect of cardiopulmonary bypass. Blood 1993; 82: 107-17.
    CrossrefPubMedGoogle Scholar
  • 33 Mangano DT. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002; 347: 1309-17.
    CrossrefPubMedGoogle Scholar
  • 34 Chesebro JH, Fuster V, Elveback LR. et al Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. N Engl J Med 1984; 310: 209-14.
    CrossrefPubMedGoogle Scholar
  • 35 Oba J, Shiiya N, Matsui Y. et al Alterations in coagulation and fibrinolysis after surgery for aortic aneurysm. Surg Today 1995; 25: 532-5.
    CrossrefPubMedGoogle Scholar
  • 36 Samama CM, Thiry D, Elalamy I. et al Perioperative activation of hemostasis in vascular surgery patients. Anesthesiology 2001; 94: 74-8.
    CrossrefPubMedGoogle Scholar
  • 37 Lo B, Fijnheer R, Castigliego D. et al Activation of hemostasis after coronary artery bypass grafting with or without cardiopulmonary bypass. Anesth Analg 2004; 99: 634-40.
    CrossrefPubMedGoogle Scholar
  • 38 Bottiger BW, Snyder-Ramos SA, Lapp W. et al Association between early postoperative coagulation activation and peri-operative myocardial ischaemia in patients undergoing vascular surgery. Anaesthesia 2005; 60: 1162-7.
    CrossrefPubMedGoogle Scholar
  • 39 Lindberg L, Forsell C, Jogi P. et al Effects of dexamethasone on clinical course, C-reactive protein, S100B protein and von Willebrand factor antigen after paediatric cardiac surgery. Br J Anaesth 2003; 90: 728-32.
    CrossrefPubMedGoogle Scholar